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Background While much research is devoted to identifying novel biomarkers, addressing the prognostic value of routinely measured clinical parameters is of great interest. We studied early blood pressure (BP) and body weight (BW) trajectories in incident haemodialysis patients and their association with all-cause mortality. Methods In a cohort of 357 incident patients, we obtained all records of BP and BW during the first 90 days on dialysis (over 12 800 observations) and analysed trajectories using penalized B-splines and mixed linear regression models. Baseline comorbidities and all-cause mortality (median follow-up: 2.2 years) were obtained from the French Renal Epidemiology and Information Network (REIN) registry, and the association with mortality was assessed by Cox models adjusting for baseline comorbidities. Results During the initial 90 days on dialysis, there were non-linear decreases in BP and BW, with milder slopes after 15 days [systolic BP (SBP)] or 30 days [diastolic BP (DBP) and BW]. SBP or DBP levels at dialysis initiation and changes in BW occurring in the first month or during the following 2 months were significantly associated with survival. In multivariate models adjusting for baseline comorbidities and prescriptions, higher SBP value and BW slopes were independently associated with a lower risk of mortality. Hazard ratios of mortality and 95% confidence intervals were 0.92 (0.85–0.99) for a 10 mmHg higher SBP and 0.76 (0.66–0.88) for a 1 kg/month higher BW change on Days 30–90. Conclusions BW loss in the first weeks on dialysis is a strong and independent predictor of mortality. Low BP is also associated with mortality and is probably the consequence of underlying cardiovascular diseases. These early markers appear to be valuable prognostic factors.

International audience; We describe the first case of distal renal tubular acidosis (dRTA) associated with primary sclerosing cholangitis. A 26-year-old Lao-Thai male patient presented with severe jaundice, metabolic acidosis and hypokalaemia. He was diagnosed of dRTA. Liver transplantation resulted in correction of electrolyte disturbances and hyperbilirubinaemia. A fludrocortisone-furosemide test revealed normal urinary acidification, demonstrating no residual dRTA. This observation suggests that dRTA may be an early manifestation of bilirubin-associated nephropathy or the consequence of an immune mechanism.

International audience; More than 840 million people, representing almost 10% of world population, were estimated to have chronic kidney disease (CKD) in 2017. In CKD, many systemic changes relative to oxidative stress, inflammation, energy balance or neuroendocrine signalling are observed and can be linked to dysfunctional proteins, including protein post-translational modifications (PTMs). Recent technical advances enabled the detection of PTMs and allowed understanding their participation in CKD pathophysiology and kidney damage. In this review article, the interconnections between CKD and PTMs, both as causes and consequences, are described. PTMs, particularly non-enzymatic PTMs, are frequently observed in CKD, as they are the direct consequence of systemic changes following the decline in kidney function. Other PTMs, mainly enzymatic ones, are critical for proper kidney physiology. Still, both types of PTMs have been shown to induce damage not only in kidney but also in other organs (brain, cardiovascular system). Therapeutic approaches focusing on metabolic changes responsible for PTMs alteration have shown interesting results. Targeting specific PTMs responsible for kidney damage is also being considered, which could lead to the development of innovative treatments.

International audience; Haemolytic uraemic syndrome (HUS) is a rare complication of invasive infection by Streptococcus pneumoniae (SP-HUS), especially in adults. Here we report an unusual case of a 53-year-old man presenting SP-HUS with severe multivisceral involvement. After failure of supportive care and plasma exchanges, eculizumab (anti-C5 antibody) resulted in a favourable outcome.

International audience; Since 1973, a few cases of concomitant inflammatory demyelinating polyradiculoneuropathy and nephrotic syndrome have been reported. The neuropathy was either an acute inflammatory demyelinating polyneuropathy (AIDP) or a chronic inflammatory demyelinating polyneuropathy (CIDP), and the nephrotic syndrome was related to either a focal segmental glomerulosclerosis (FSGS) or a membranous glomerulonephritis (MGN).Time course, severity, and response to treatment were heterogeneous, and evolution of neuropathy and nephropathy could be independent. This suggests that common epitopes are targeted by autoantibodies within the peripheral nerve and the glomerular filtration barrier. However, the antigenic targets are unknown. Here, we report a patient who developed CIDP associated with anti-contactin-1 immunoglobulin G4 (IgG4) antibodies and nephrotic syndrome.

International audience; Background: Various alterations in lipid metabolism have been observed in patients with chronic kidney disease (CKD).Objectives: To determine the levels of lipid species in plasma from CKD and hemodialysis (HD) patients and test their association with CKD severity and patient outcome.Methods: Seventy-seven patients with CKD stage 2 to HD were grouped into classes of CKD severity at baseline and followed-up for 3.5 years for the occurrence of transition to HD or death (combined outcome). Plasma levels of phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), sphingomyelins (SMs), and fatty acids were analyzed by flow-injection analysis coupled to tandem mass spectrometry or gas chromatography coupled with mass spectrometry. Kruskal Wallis rank tests and Cox regressions were used to analyze the association of lipids with CKD severity and the risk of combined outcome, respectively.Results: The plasma level of PCs, LPCs, and SMs was decreased in HD patients compared with nondialyzed CKD patients (all P < .05), whereas esterified and/or nonesterified fatty acids level did not change. Thirty-four lipids displayed significantly lower abundance in plasma of HD patients, whereas elaidic acid (C18:1ω9t) level was increased (P < .001). The total amount of LPCs and individual LPCs were associated with better outcome (P < .05). In particular, LPC 18:2 and LPC 20:3 were statistically associated with outcome in adjusted models (P < .05).Discussion: In HD patients, a reduction in plasma lipids is observed. Some of the alterations, namely reduced LPCs, were associated with the risk of adverse outcome. These changes could be related to metabolic dysfunctions.

BACKGROUND: \ud \ud The reduced glomerular filtration rate in the advanced stages of chronic kidney disease (CKD) leads to plasma accumulation of uraemic retention solutes including proteins. It has been hypothesized that these changes may, at least in part, be responsible for CKD-associated morbidity and mortality. However, most studies focused on the role of individual proteins, while a holistic, large-scale, integrative approach may generate significant additional insight.\ud \ud METHODS: \ud \ud In a discovery study, we analysed the plasma proteome of patients with stage 2-3 CKD (n = 14) and stage 5 CKD with haemodialysis (HD) (n = 15), using high-resolution LC-MS/MS analysis. Selected results were validated in a cohort of 40 patients with different CKD stages with or without HD, using ELISA.\ud \ud RESULTS: \ud \ud Of a total of 2054 detected proteins, 127 displayed lower, while 206 displayed higher abundance in the plasma of patients on HD. Molecular pathway analysis confirmed the modification of known processes involved in CKD complications, including decreased haemostasis and increased inflammation, complement activation and vascular damage. In addition, we identified the plasma increase during CKD progression of lysozyme C and leucine-rich alpha-2 glycoprotein, two proteins related to vascular damage and heart failure. High level of leucine-rich alpha-2 glycoprotein was associated with higher mortality in stage 5 CKD patients on HD.\ud \ud CONCLUSIONS: \ud \ud This study provides for the first time a comprehensive assessment of CKD plasma proteome, contributing to new knowledge and potential markers of CKD. These results will serve as a basis for future studies investigating the relevance of these molecules in CKD associated morbidity and mortality.

Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±-0.065; P

Seasons and climate influence the regulation of blood pressure (BP) in the general population and in hemodialysis patients. It is unknown whether this phenomenon varies across the world. Our objective was to estimate BP seasonality in hemodialysis patients from different geographical locations. Patients from 7 European countries (Spain, Italy, France, Belgium, Germany, United Kingdom, and Sweden) participating in the DOPPS (Dialysis Outcomes and Practice Patterns Study) on years 2005 to 2011 were studied. Factors influencing pre- and postdialysis systolic BP and diastolic BP levels were analyzed by mixed models. There were 9655 patients (median age, 68; 59% male) from 263 facilities, seen every 4 months during a median duration of 1.3 years. Pre- and postdialysis systolic BP increased by a mean estimate of 5.1 mm Hg (95% confidence interval [CI], 3.7–6.4 mm Hg) and 4.4 mm Hg (95% CI, 2.9–5.9 mm Hg) for each 10° increase in latitude (1111 km to the North). In the longitudinal analysis, predialysis systolic BP was lower in summer and higher in winter (difference, 1.7 mm Hg; 95% CI, 1.3–2.2 mm Hg), with greater differences in southern locations ( P interaction =0.04). Predialysis systolic BP was inversely associated with outdoor temperature (−0.8 mm Hg/7.2°C; 95% CI, −1.0 to −0.5 mm Hg/7.2°C), with steeper slopes in southern locations ( P interaction =0.005). Results were similar for predialysis diastolic BP. In conclusion, there is a geographical and seasonal gradient of BP in European hemodialysis patients. There is a need to consider these effects when evaluating and treating BP in this population and potentially in others.

Background Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273). Methods In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier. Results We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found. Conclusion We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial

International audience; Introduction: Recent randomised controlled trials suggest that on-line hemodiafiltration (OL-HDF) improves survival, provided that it reaches high convective volumes. However, there is scant information on the feasibility and the consequences of modifying convection volumes in clinics.Methods: Twelve stable dialysis patients were treated with high-flux 1.8 m2 polysulphone dialyzers and 4 levels of convection flows (QUF) based on GKD-UF monitoring of the system, for 1 week each. The consequences on dialysis delivery (transmembrane pressure (TMP), number of alarms, % of achieved prescribed convection) and efficacy (mass removal of low and high molecular weight compounds) were analysed.Results: TMP increased exponentially with QUF (p56,000 monitoring values). Beyond 21 L/session, this resulted into frequent TMP alarms requiring nursing staff interventions (mean ± SEM: 10.3 ± 2.2 alarms per session, p 20L) is feasible by setting an HDF system at its optimal conditions based upon the GKD-UF monitoring. Prescribing higher convection volumes resulted in instability of the system, provoked alarms, was bothersome for the nursing staff and the patients, rarely achieved the prescribed convection volumes and increased removal of high molecular weight compounds, notably albumin.

Jean Batiste von Helmont (1577-1644) described a salt that "never occurs outside man's body". The substance was further characterized by Hermann Boerhaave from Leiden (1688-1738) in Elementa Chemiae where he described the whole procedure for isolating it from urine of healthy persons. The French scientists Fourcroy and Vauquelin, in 1808, named it "ure" whereas Jean-Etienne Brard from Montpellier established its chemical composition in 1817. The synthesis of urea was accomplished by Friedrich Whler (the first organic substance to be synthesized). Finally in 1851 Friedrich Th. von Frerichs introduced the term "Uraemia".

International audience

International audience; In 2011, Nephrology Dialysis and Transplantation (NDT) established a more restrictive selection process for manuscripts submitted to the journal, reducing the acceptance rate from 25% (2008-2009) to currently about 12-15%. To achieve this goal, we decided to score the priority of manuscripts submitted to NDT and to reject more papers at triage than in the past. This new scoring system allows a rapid decision for the authors without external review. However, the risk of such a restrictive policy may be that the journal might fail to capture important studies that are eventually published in higher-ranked journals. To look into this problem, we analysed random samples of papers (∼10%) rejected by NDT in 2012. Of the papers rejected at triage and those rejected after regular peer review, 59 and 61%, respectively, were accepted in other journals. A detailed analysis of these papers showed that only 4 out of 104 and 7 out of 93 of the triaged and rejected papers, respectively, were published in journals with an impact factor higher than that of NDT. Furthermore, for all these papers, independent assessors confirmed the evaluation made by the original reviewers. The number of citations of these papers was similar to that typically obtained by publications in the corresponding journals. Even though the analyses seem reassuring, previous observations made by leading journals warn that the risk of 'big misses', resulting from selective editorial policies, remains a real possibility. We will therefore continue to maintain a high degree of alertness and will periodically track the history of manuscripts rejected by NDT, particularly papers that are rejected at triage by our journal.

In the early 1700s, a substance ultimately identified as urea was reported for the first time in urine. About a century later, in 1828, synthesis of this organic compound was achieved, thus giving rise to modern organic chemistry. In parallel, physicians showed that urine comes from the kidneys and contains large amounts of urea, which is produced outside of the kidneys, establishing the humoral approach of renal physiology. Urea was the first uremic retention solute to be identified and it has been used as a marker of renal disease ever since. However, progress in the knowledge of urea metabolism has shown that it is susceptible to many extrarenal variations and, therefore, it cannot be a reliable marker of renal function. It reflects protein intake in the stable patient and has been used to assess nutrition and dialysis efficacy in renal patients. Although it has been studied for almost 200 years, its toxicity has been largely debated. An indirect toxicity occurring through carbamylation of lysine residues is now well established and some evidence from recent work also supports direct toxicity of urea, offering additional rationale for interventional prevention of uremic complications.

Although a wide range of physical principles capable of separating different solutes exist in biochemistry (such as affinity, or size as well as charge retaining columns and others), the removal of uraemic solutes has been almost exclusively performed up to the present with membrane-based systems. Sir Thomas Graham, in the second half of the 1800s, defined the method of separating various fluids by diffusion through a membrane with the term ‘dialysis’[1]. Galen in the second century of our era already claimed that the skin resembles a sieve and ‘sweating purifies the body, … by low-effort exercise, baths and the summer heat’ [De Symptomatum Causis Libri III, Claudii Galeni Opera Omnia (II)][2], and ancient Romans used the skin as a natural membrane to rid their bodies of poisonous urinal substances in the Therms and public baths. Well into the 20th century, artificial kidneys, based on membrane devices were adopted and the pioneer work by Abel, Rowntree and Turner [3], as well as that of Haas [4], was followed by the rotatory drum dialyser of Willem Kolff [5] and the vertical drum one of Nils Alwall [6]. Finally, the hollow fibre dialysers gained adepts and a widespread use of cuprophane membranes for a very long period of time (from the 1970s to the 1990s) has been followed by the introduction of high-flux membranes that have invaded most of the dialysis units worldwide to the present. It became quite clear from the very beginning that membranes differ in their clearance capacities of the different solutes, basically depending on thickness and pore size. However, increasing the pore size and reducing thickness is almost forcedly associated to a water permeability increase. The open dialysate circuit settings used during the era of low-permeability membranes had to be secured by the addition of ultrafiltration controllers, which closed the dialysis circuit [7], and are mandatory when using high-flux membranes (highly permeable to water) particularly if convective techniques are utilized. Defining water permeability of a dialyser was considered important from the beginning and is even more important with the high-flux dialysers. Water permeability of a dialyser was defined by its ultrafiltration coefficient, which is displayed in the notice of the given dialyser. The coefficient of ultrafiltration (KUF) was first defined by the amount of fluid (V) in mL crossing the dialyser membrane per time (T) in hours and pressure (P) in mmHg: KUF=VT×P The perception that renal physicians have of KUF has changed over time. Senior nephrologists considered KUF as a constant and took it into account in dialysis prescription in the low-permeability era [8]; it was common to hear comments on the different KUF or ‘slope’ of one dialyser in regard to another one in clinics and the consequences that this might have to the treatment and to the patient. Among senior physicians, only those particularly interested on the topic knew that KUF was not always a constant as its value may vary over a certain range of filtration rate. Young nephrologists, who have only lived the ultrafiltration controller era, have just ignored KUF. They simply did not need it. Nevertheless, the importance of KUF of the early times has remained in many aspects, including the approval of new devices by the regulatory agencies such as the US Food and Drugs Administration (FDA) [9] or its equivalent in Europe, the European Medicines Agency (EMA), a prerequisite to use them in clinics in all these countries. Indeed, the recent randomized, controlled trials on haemodiafiltration [10–12] and particularly that of Maduell et al. [12] providing evidence that high convective volume may improve survival has given a renewed protagonism to KUF, as it influences the convective capacities of the dialysis setting. KUF remains, though, the old ‘grand inconnu’. In the present editorial comment, we want to present a refurbished KUF to society, going in-depth into the factors influencing KUF and its calculation, and then coming back with as simple as possible methods to obtain it for easy clinical use.

International audience; Chronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms. To test this approach, we examined samples from a cohort of 49 patients representing different stages of CKD. Urine samples were analysed for proteomic changes using capillary electrophoresis-mass spectrometry and urine and plasma samples for metabolomic changes using different mass spectrometry-based techniques. The training set included 20 CKD patients selected according to their estimated glomerular filtration rate (eGFR) at mild (59.9616.5 mL/min/1.73 m 2 ; n = 10) or advanced (8.964.5 mL/min/1.73 m 2 ; n = 10) CKD and the remaining 29 patients left for the test set. We identified a panel of 76 statistically significant metabolites and peptides that correlated with CKD in the training set. We combined these biomarkers in different classifiers and then performed correlation analyses with eGFR at baseline and follow-up after 2.860.8 years in the test set. A solely plasma metabolite biomarker-based classifier significantly correlated with the loss of kidney function in the test set at baseline and follow-up (r = 20.8031; p,0.0001 and r = 20.6009; p = 0.0019, respectively). Similarly, a urinary metabolite biomarker-based classifier did reveal significant association to kidney function (r = 20.6557; p = 0.0001 and r = 20.6574; p = 0.0005). A classifier utilising 46 identified urinary peptide biomarkers performed statistically equivalent to the urinary and plasma metabolite classifier (r = 20.7752; p,0.0001 and r = 20.8400; p,0.0001). The combination of both urinary proteomic and urinary and plasma metabolic biomarkers did not improve the correlation with eGFR. In conclusion, we found excellent association of plasma and urinary metabolites and urinary peptides with kidney function, and disease progression, but no added value in combining the different biomarkers data.

International audience; Toxoplasma infection is uncommon after renal transplantation. As a result, Toxoplasma gondii is often missed from the list of microbial agents which may be responsible of an infectious complication after renal transplantation. However, establishing this diagnosis is very important because toxoplasmosis can be life-threatening in an immunocompromised host, particularly when the diagnosis is too delayed. Here we report two cases of severe toxoplasmosis after renal transplantation. In the first case, primary infection transmitted by a cat developed in a seronegative recipient five years after renal transplantation. In the second case, reactivation of latent infection developed in a seropositive recipient 9 months after transplantation. In both cases, systematic screening for Toxoplasma gondii using polymerase chain reaction (PCR) in biological fluids was essential to suggest the diagnosis. Both recipients rapidly recovered after institution of antiparasitic therapy.